The impact of endocrine-disrupting chemicals on stem cells: Mechanisms and implications for human health.

Endocrine-disrupting chemicals (EDCs) are compounds, either natural or man-made, that interfere with the normal functioning of the endocrine system. There is increasing evidence that exposure to EDCs can have profound adverse effects on reproduction, metabolic disorders, neurological alterations, and increased risk of hormone-dependent cancer. Stem cells (SCs) are integral to these pathological processes, and it is therefore crucial to understand how EDCs may influence SC functionality. This review examines the literature on different types of EDCs and their effects on various types of SCs, including embryonic, adult, and cancer SCs. Possible molecular mechanisms through which EDCs may influence the phenotype of SCs are also evaluated. Finally, the possible implications of these effects on human health are discussed. The available literature demonstrates that EDCs can influence the biology of SCs in a variety of ways, including by altering hormonal pathways, DNA damage, epigenetic changes, reactive oxygen species production and alterations in the gene expression patterns. These disruptions may lead to a variety of cell fates and diseases later in adulthood including increased risk of endocrine disorders, obesity, infertility, reproductive abnormalities, and cancer. Therefore, the review emphasizes the importance of raising broader awareness regarding the intricate impact of EDCs on human health.

Weight Loss Differentially Impacts Sex Hormones in Women and Men with Type 2 Diabetes: Look AHEAD Sex Hormone Study.

BACKGROUND: Despite sex differences in T2D, few studies have examined the role of sex hormones. We sought to assess the impact of weight loss, the cornerstone of T2D management, on sex hormone levels. METHODS: This was an ancillary study to the Look AHEAD (Action for Health In Diabetes) Study (n=850 postmenopausal females, n=890 males, with T2D and BMI ≥25 kg/m2). We measured total testosterone (T), estradiol (E2) and sex hormone binding globulin (SHBG) and calculated bioavailable T (bioT). We examined the effect of the intensive lifestyle intervention (ILI) on hormone changes, whether changes were mediated by waist circumference and sex differences in treatment effect. RESULTS: The baseline mean age was 60 years with a higher proportion of Black females (21%) vs. males (9%) and higher mean BMI in females vs. males (36.3 vs. 34.8 kg/m2). At year 1 in females, ILI decreased E2 by 15% and bioT by 13% and increased SHBG by 21%. At year 1 in males, ILI did not change E2 levels, but increased T by 14% and increased SHBG by 18%. The effect was attenuated over 4 years, there were statistically significant sex differences in treatment effect and change in waist circumference due to ILI at year 1 was a significant mediator of sex hormone changes. CONCLUSION: Weight loss in T2D resulted in sex hormone changes, which varied by sex and were mediated by changes in WC. Changes in sex hormone due to weight loss in T2D should be considered in the context of an individual's health risks, including cardiovascular, bone health, menopausal symptoms and cognition.

Potential Predictor of Epigenetic Age Acceleration in Men: 2D:4D Finger Pattern.

OBJECTIVES: Second to fourth digit ratio is widely known indicator of prenatal sex hormones proportion. Higher prenatal androgenization results in longer fourth finger and lower 2D:4D index. The aim of this study was to determine whether the 2D:4D digit ratio is associated with DNA methylation (DNAm) age dependently on sex. MATERIAL AND METHODS: The study included 182 adults (106 females and 76 males) with a mean age of 51.5 ± 13 years. The investigation consisted of three main parts: a survey, anthropometric dimensions measurements (fingers length) and methylome analysis using collected blood samples. Genome-wide methylation was analyzed using EPIC microarray technology. Epigenetic age and epigenetic age acceleration were calculated using several widely applied algorithms. RESULTS: Males with the female left hand pattern had more accelerated epigenetic age than those with the male pattern as calculated with PhenoAge and DNAmTL clocks. CONCLUSIONS: Finger female pattern 2D:4D above or equal to 1 in males is associated with epigenetic age acceleration, indicating that prenatal exposure to estrogens in males may be related to aging process in the later ontogenesis.

A validated HPLC-MS/MS method for the simultaneous determination of ecdysteroid hormones in subminimal amounts of biological material.

Ecdysteroids represent a large class of polyhydroxylated steroids which, due to their anabolic properties, are marketed as dietary supplements. Some ecdysteroids also act as important hormones in arthropods, where they regulate molting, development, and reproduction and many of these insects are miniature organisms that contain submicroliter levels of circulating biofluids Analysis of ecdysteroids is further complicated by their very low abundance, large fluctuations during development, and difficult access to a pooled sample, which is important for quantitative measurements. In this work, we propose a new method that overcomes the described difficulties and allows validated quantification of four ecdysteroids in minimal amounts of biological material. After methanolic extraction, detectability of the ecdysteroids is increased 16- to 20-fold by conversion to their 14,15-anhydrooximes. These are further purified by pipette tip solid phase extraction (PT-SPE) on a three-layer sorbent and subjected to HPLC-MS/MS analysis. Full validation was achieved using hemolymph from larvae of the firebug Pyrrhocoris apterus as a blank matrix and by the determination of ecdysteroids in a single Drosophila larva. The LLOQs for the four target ecdysteroids (20-hydroxyecdysone, ecdysone, makisterone A, and 2-deoxyecdysone) were 0.01; 0.1; 0.05; 0.025 pg·mL-1 (20; 200; 100; 50 fmol·mL-1) respectively, with very good accuracy, precision (RSD < 15%) and recoveries (96% - 119.9%).The general suitability of the new method was demonstrated by quantification of ecdysteroids in various biological materials including human serum.

Systemic Factors Affecting Pain Management in Dentistry.

There are several factors that affect a patient's experience of pain. These include both local and systemic factors. The systemic factors that affect patients' dental and orofacial pain experience include, but not limited to, hormonal, nutritional, systemic infections, neurodegenerative, and autoimmune, among others. Comprehensive medical history is essential to delineate any possible systemic factors affecting pain experience. A thorough review of systems should form the foundation, since multiple factors can affect the prognosis of pain management. This would facilitate early recognition and trigger prompt referrals to the appropriate medical professionals. This helps to reduce the health care burden.

Psychotic symptoms in Chinese adolescent patients with major depressive disorder: prevalence and related endocrine clinical factors.

OBJECTIVE: Major depressive disorder (MDD) is often accompanied by psychotic symptoms. However, few studies have examined the relationship between psychotic symptoms and endocrine factors in adolescent patients with MDD. Therefore, this study aimed to investigate the prevalence and related endocrine clinical factors of psychotic symptoms in Chinese adolescent patients with MDD. METHODS: In total, 601 patients (aged 12-18) with MDD were recruited. The Patient Health Questionnaire - 9 items (PHQ - 9) was utilized for assessing depressive symptoms. Psychotic symptoms were assessed through clinical interviews. Prolactin (PRL), thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3), thyroxine (T4), and free thyroxine (FT4) were also measured. RESULTS: The incidence of psychotic symptoms in adolescent patients with MDD was 22.6%. The findings demonstrated that age, self-harming behavior, PHQ-9 score, FT4, and normalized PRL were independently associated with psychotic symptoms in patients with MDD (All p < 0.05). CONCLUSIONS: PRL and FT4 levels are more likely to be abnormally elevated in major depressive adolescents with psychotic symptoms. Prolactin and thyroid hormones in patients with MDD should be paid more attention.

Moonlighting Crypto-Enzymes and Domains as Ancient and Versatile Signaling Devices.

Increasing numbers of reports have revealed novel catalytically active cryptic guanylate cyclases (GCs) and adenylate cyclases (ACs) operating within complex proteins in prokaryotes and eukaryotes. Here we review the structural and functional aspects of some of these cyclases and provide examples that illustrate their roles in the regulation of the intramolecular functions of complex proteins, such as the phytosulfokine receptor (PSKR), and reassess their contribution to signal generation and tuning. Another multidomain protein, Arabidopsis thaliana K+ uptake permease (AtKUP5), also harbors multiple catalytically active sites including an N-terminal AC and C-terminal phosphodiesterase (PDE) with an abscisic acid-binding site. We argue that this architecture may enable the fine-tuning and/or sensing of K+ flux and integrate hormone responses to cAMP homeostasis. We also discuss how searches with motifs based on conserved amino acids in catalytic centers led to the discovery of GCs and ACs and propose how this approach can be applied to discover hitherto masked active sites in bacterial, fungal, and animal proteomes. Finally, we show that motif searches are a promising approach to discover ancient biological functions such as hormone or gas binding.

Thyroid hormones and oxidative stress moderated the association between urinary phthalate metabolites and cardiovascular risk factors.

While previous studies suggested that phthalate exposure poses a risk to cardiovascular health, the results are mixed and indicated variability based on population characteristics and health outcomes assessed. Research that simultaneously investigates the association between urinary phthalate metabolites and multiple cardiovascular risk factors within a single study is relatively scarce. This study assessed human exposure to phthalates by determining urinary metabolite concentrations, and applied multiple statistical techniques to systematically evaluate the individual dose-response relationships and joint effects of phthalate exposure on blood lipids, blood pressure, and fasting blood glucose. The results revealed significant negative associations between urinary phthalate metabolites and low-density lipoprotein cholesterol, triglycerides, total cholesterol, diastolic blood pressure, systolic blood pressure, and fasting blood glucose. Significant nonlinear associations were obtained between specific individual metabolites and diastolic blood pressure. The oxidative stress biomarker 8-hydroxydeoxyguanosine levels in urine and thyroid hormone levels in paired serum were measured simultaneously. Then, we examined the indirect roles of thyroid hormones and oxidative stress in the association between urinary phthalate metabolites and cardiovascular risk factors by mediation and moderation analysis. While the mediation effect was not statistically significant, the negative associations of urinary phthalate metabolites with fasting blood glucose, triglyceride, and lipoprotein cholesterol were statistically significant at lower levels of thyroid hormones by moderation analysis. The association was also significant under certain levels of oxidative stress. The results demonstrated that phthalate exposure is associated with several cardiovascular risk factors, and maintaining appropriate oxidative stress levels and ensuring sufficient thyroid hormone levels may attenuate these associations.

Anabolic steroid consumption among gym-goers in Amman: knowledge, attitudes, and behaviors.

Background: The use of Anabolic-androgenic steroids (AAS) among gym members has become a significant concern due to their impact on physical training and performance. Research worldwide indicates a notable prevalence of AAS use among athletes and gym attendees, often involving substances that are neither safe nor legal. Objectives: This study aims to determine the prevalence of AAS use among gym attendees in Amman, Jordan, and to explore the knowledge, attitudes, and behaviors associated with AAS use. Methods: The study involved 399 participants from 35 randomly selected gyms in the metropolitan area of Amman, Jordan. A cluster sampling technique was used to select a diverse and representative sample of gym attendees. Data was collected using a self-administered questionnaire that assessed AAS use, knowledge, attitudes, and behavioral factors. Statistical analyses were conducted using chi-square tests to explore the relationships between AAS use and categorical variables, while logistic regression was employed to identify predictors of AAS use. Results: The analysis revealed significant associations between AAS use and various factors, including knowledge, attitudes, behavioral factors, and demographic variables such as gender, age, exercise frequency, reasons for exercise, and total exercise duration. The study identified key predictors of AAS use among gym attendees in Amman, highlighting the importance of demographic and behavioral factors. Conclusion: The findings underscore the need for targeted interventions to address misconceptions and promote safer practices among gym-goers in Amman. The study provides critical insights that can guide the development of strategies, policy adjustments, and educational initiatives aimed at reducing AAS misuse and fostering a healthier gym culture in the region.

Imaging the spatial distribution of structurally diverse plant hormones: A comprehensive review.

Plant hormones are essential and structurally diverse molecules that regulate various aspects of plant growth, development, and stress responses. However, the precise analysis of plant hormones in complex biological samples poses a challenge due to their low concentrations, dynamic levels, and intricate spatial distribution. Moreover, the complexity and interconnectedness of hormone signaling networks make it difficult to simultaneously trace multiple hormone distributions. In this review, we provide an overview of the currently recognized small-molecule plant hormones, signal peptide hormones, and plant growth regulators, along with the analytical methods employed for their analysis. We delve into the latest advancements in mass spectrometry imaging and in situ fluorescence techniques, which enable the examination of the spatial distribution of plant hormones. The advantages and disadvantages of these imaging techniques are further discussed. Finally, we propose potential avenues for future research in this field to further enhance our understanding of plant hormone biology.

Joint effects of tobacco smoke exposure and heavy metals on serum sex hormones in adult males.

OBJECTIVE: This study aimed to explore the associations of tobacco smoke exposure (TSE) and heavy metal exposure on sex hormones and the joint effects between them in adult males. METHODS: The study used data of 2244 adult males from the National Health and Nutrition Examination Survey (NHANES, 2013-2016). Weighted linear regression models were used to calculate their beta (ß) coefficients and corresponding confidence interval (95% CI), which assessed the joint effects of TSE and heavy metals on sex hormones. RESULTS: Sex hormone-binding globulin (SHBG) showed a positive association with increased per standard deviation (SD) for cotinine (ß=0.024 [0.004, 0.043]; P<0.001), lead (ß=0.021 [0.002, 0.039]; P=0.028), and cadmium (ß=0.034 [0.015, 0.053]; P<0.001). Manganese was positively associated with estradiol (E2) (ß=0.025 [0.009, 0.042]; P=0.002). The subjects with higher cadmium levels were more likely to have higher total testosterone (TT) (ß=0.042 [0.023, 0.062]; P<0.001). TSE and lead exerted synergistic effects on TT (p for interaction = 0.015) and E2 (p for interaction = 0.009), as also did TSE and cadmium on SHBG (p for interaction = 0.037). Compared with the reference group, TSE participants who were exposed to high concentrations of lead, cadmium, mercury, and manganese had significantly elevated TT levels, but these high levels presented no significant association with E2 levels. A significantly higher level of SHBG among TSE participants was detected in high concentrations for lead, cadmium, and mercury. CONCLUSION: TSE exacerbated sex hormone imbalances when combined with high levels of metal exposure. Smoking cessation is crucial, especially in the case of high levels of occupational exposure to heavy metals.

Appetite hormones, neuropsychological function and methylphenidate use in children with attention-deficit/hyperactivity disorder.

Appetite hormones may play a significant role in neuronal excitability and synaptic plasticity and may also affect brain function development. This study aimed to explore the role of appetite hormones in attention deficit/hyperactivity disorder (ADHD), including aspects of pathophysiology, pharmacotherapy, and side effects. We recruited 119 patients with ADHD who were undergoing methylphenidate treatment (ADHD+MPH), 77 unmedicated ADHD patients (ADHD-MPH), and 87 healthy controls. Blood samples were collected from all participants to examine serum levels of orexin A, ghrelin, leptin, and adiponectin. Behavioral symptoms were assessed using the Swanson, Nolan, and Pelham Rating Scale, and visual and auditory attention were evaluated using computerized neuropsychological tests. The side effects of methylphenidate treatment were measured using Barkley's Side Effects Rating Scale. Orexin levels in the control group were significantly higher than in the ADHD-MPH (p=0.037) and ADHD+MPH (p<0.001) groups; additionally, orexin levels in the ADHD-MPH group were significantly higher than in the ADHD+MPH group (p=0.032). Leptin levels in both the ADHD+MPH (p=0.011) and ADHD-MPH (p=0.011) groups were significantly lower than in the control group. Ghrelin levels were positively associated with auditory attention across all ADHD groups (p=0.015). Furthermore, ghrelin levels were positively correlated with methylphenidate dosage (p=0.024), and negatively correlated with methylphenidate side effects (p=0.044) in the ADHD+MPH group. These findings provide further insight into the relationships between appetite hormones, pharmacotherapy, and ADHD. Orexin A and leptin are associated with the etiology of ADHD, while orexin A and ghrelin play important roles in attention deficits and methylphenidate usage in ADHD.

Effects of time-restricted eating and low-carbohydrate diet on psychosocial health and appetite in individuals with metabolic syndrome: A secondary analysis of a randomized controlled trial.

BACKGROUND & AIMS: Time-restricted eating (TRE) and low-carbohydrate diet (LCD) can improve multiple cardiometabolic parameters in patients with metabolic syndrome (MetS), but their effects on psychosocial health and satiety are unclear. In this study, we aimed to evaluate the effects of TRE, LCD, and their combination (TRE + LCD) on quality of life (QoL), sleep, mood, appetite, and metabolic hormones in patients with MetS. METHODS: This is a secondary analysis of a single-center, 3-month, open-label, randomized clinical trial investigating the effects of TRE, LCD, and TRE + LCD on weight and cardiometabolic parameters in individuals with MetS. This secondary analysis examined QoL, sleep, mood, and appetite using the Rand 36-Item Short Form (SF-36); Pittsburgh Sleep Quality Index (PSQI); Depression, Anxiety, and Stress Scale; and Eating Behavior Rating Scale, respectively, as well as measured levels of metabolic hormones including leptin, amylin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1 (GLP-1), pancreatic polypeptide (PP), and peptide YY. Between-group comparisons were conducted via one-way ANOVAs and post hoc LSD tests for normally distributed variables or Kruskal‒Wallis H tests and the Nemenyi test for abnormally distributed variables. P < 0.017 was considered significant in multiple comparisons following Bonferroni adjustment. RESULTS: A total of 162 participants (mean [SD] age, 41.2 [9.9] years; mean [SD] body mass index, 29.3 [3.4] kg/m2; 102 [63%] men) who started the intervention were analyzed. After 3 months, only the TRE group decreased GLP-1 levels (-0.9 [IQR, -1.9 to -0.3] pg/mL; P = 0.002), increased PP levels (8.9 [IQR, -7.6 to 71.8] pg/mL; P = 0.011), physical functioning in the SF-36 (5.2 [95% CI, 1.9 to 8.5]; P = 0.001), social functioning in the SF-36 (9.1 [95% CI, 2.5 to 15.6]; P = 0.005), role-physical in the SF-36 (24.1 [95% CI, 11.8 to 36.4]; P < 0.001), role-emotional in the SF-36 (22.4 [95% CI, 12.6 to 32.2]; P < 0.001), and sleep efficiency in the PSQI (0.29 [95% CI, 0.03 to 0.55]; P = 0.021). Compared with changes in LCD, TRE further increased general health in the SF-36 (9.7 [95% CI, 3.3 to 16.0]; P = 0.006). Relative to the changes of TRE + LCD, TRE significantly increased role-emotional in the SF-36 (19.9 [95% CI 4.9 to 34.8]; P = 0.006). Changes in sleep quality, mood status, appetite, and metabolic hormones did not differ among three groups. Greater weight loss was associated with decreased leptin levels (r = 0.538), decreased amylin levels (r = 0.294), reduced total appetite scores (r = 0.220), and improved general health (r = -0.253) (all P ≤ 0.01). CONCLUSIONS: TRE, LCD, and TRE + LCD all could improve psychosocial health and reduce appetite. Notably, TRE yielded greater benefits in QoL compared with LCD or TRE + LCD in individuals with MetS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04475822.

The association between testosterone, estradiol, estrogen sulfotransferase and idiopathic pulmonary fibrosis: a bidirectional mendelian randomization study.

BACKGROUND: The causal relationships between testosterone, estradiol, estrogen sulfotransferase, and idiopathic pulmonary fibrosis (IPF) are not well understood. This study employs a bidirectional two-sample Mendelian Randomization (MR) approach to explore these associations. METHODS: All genetic data utilized in our study were obtained from the IEU Open GWAS project. For the MR analysis, we employed the inverse variance weighted (IVW), MR-Egger, and weighted median methods to assess the causal relationships. We also conducted a multivariate MR (MVMR) analysis, with adjustments made for smoking. To ensure the robustness of our findings, sensitivity analyses were conducted using Cochran's Q test, MR-Egger regression, the MR-PRESSO global test, and the leave-one-out method. RESULTS: Genetically predicted increases in serum testosterone levels by one standard deviation were associated with a 58.7% decrease in the risk of developing IPF (OR = 0.413, PIVW=0.029, 95% CI = 0.187 ∼ 0.912), while an increase in serum estrogen sulfotransferase by one standard deviation was associated with a 32.4% increase in risk (OR = 1.324, PIVW=0.006, 95% CI = 1.083 ∼ 1.618). No causal relationship was found between estradiol (OR = 1.094, PIVW=0.735, 95% CI = 0.650 ∼ 1.841) and the risk of IPF. Reverse MR analysis did not reveal any causal relationship between IPF and testosterone (OR = 1.001, PIVW=0.51, 95% CI = 0.998 ∼ 1.004), estradiol (OR = 1.001, PIVW=0.958, 95% CI = 0.982 ∼ 1.019), or estrogen sulfotransferase (OR = 0.975, PIVW=0.251, 95% CI = 0.933 ∼ 1.018). The MVMR analysis demonstrated that the association between testosterone (OR = 0.442, P = 0.037, 95% CI = 0.205 ∼ 0.953) and estrogen sulfotransferase (OR = 1.314, P = 0.001, 95% CI = 1.118 ∼ 1.545) and the risk of IPF persisted even after adjusting for smoking. CONCLUSIONS: Increased serum levels of testosterone are associated with a reduced risk of IPF, while increased levels of serum estrogen sulfotransferase are associated with an increased risk. No causal relationship was found between estradiol and the development of IPF. No causal relationship was identified between IPF and testosterone, estradiol, or estrogen sulfotransferase.

Hormonal influence: unraveling the impact of sex hormones on vascular smooth muscle cells.

Sex hormones play a pivotal role as endocrine hormones that exert profound effects on the biological characteristics and vascular function of vascular smooth muscle cells (VSMCs). By modulating intracellular signaling pathways, activating nuclear receptors, and regulating gene expression, sex hormones intricately influence the morphology, function, and physiological state of VSMCs, thereby impacting the biological properties of vascular contraction, relaxation, and growth. Increasing evidence suggests that abnormal phenotypic changes in VSMCs contribute to the initiation of vascular diseases, including atherosclerosis. Therefore, understanding the factors governing phenotypic alterations in VSMCs and elucidating the underlying mechanisms can provide crucial insights for refining interventions targeted at vascular diseases. Additionally, the varying levels of different types of sex hormones in the human body, influenced by sex and age, may also affect the phenotypic conversion of VSMCs. This review aims to explore the influence of sex hormones on the phenotypic switching of VSMCs and the development of associated vascular diseases in the human body.

The Release of Lipolytic Hormones during Various High-Intensity Interval and Moderate-Intensity Continuous Training Regimens and Their Effects on Fat Loss.

To investigate the release of lipolytic hormones during various high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), and their effects on fat loss. 39 young women categorized as obese (with a body fat percentage (BFP) ≥30%) were randomly allocated to one of the following groups: all-out sprint interval training (SIT, n =10); supramaximal HIIT (HIIT120, 120%V̇O2peak, n = 10); HIIT (HIIT90, 90%V̇O2peak, n = 10), or MICT, (60%V̇O2peak, n = 9) for a twelve-week observation period consisting of 3 to 4 exercise sessions per week. Serum epinephrine (EPI) and growth hormone (GH) were measured during the 1st, 20th, and 44th training sessions. Body weight (BW), body mass index (BMI), whole-body fat mass (FM) and BFP were assessed pre- and post-intervention. Following the 1st and 20th sessions, significant increases in EPI (p < 0.05) were observed post-exercise in HIIT120 and HIIT90, but not in SIT and MICT. In the 44th session, the increased EPI was found in SIT, HIIT120, and HIIT90, but not in MICT (p < 0.05). For the GH, a significant increase was observed post-exercise in all groups in the three sessions. The increased EPI and GH returned to baselines 3 hours post-exercise. After the 12-week intervention, significant reductions in FM and BFP were found in all groups, while reductions in BW and BMI were only found in the SIT and HIIT groups. Greater reductions in FM and BFP, in comparison to MICT, were observed in the SIT and HIIT groups (p < 0.05). 12-week SIT, HIIT120, and HIIT90, in comparison to MICT, were more efficacious in fat reduction in obese women, partly benefiting from the greater release of lipolytic hormones during training sessions.

The use of saliva and blood progesterone to profile the menstrual cycles of youth professional football players.

Background: Understanding individual ovarian hormone cycles and their relationship with health, performance and injuries is highly important to practitioners supporting female athletes. Venous blood sampling is the current gold standard for measuring the ovarian hormones, but the invasive nature of this method presents a major barrier in sport environments. Saliva analysis may offer an alternative method as it is non-invasive, allowing the sample to be collected "in situ", with relative ease, necessary in applied sport environments. Objective: The aims of this study were: (i) To compare the concentration of progesterone between capillary blood and saliva, (ii) To assess the efficacy of weekly measurements of progesterone for determining if ovulation has occurred in elite eumenorrheic football players, and (iii) To establish a saliva criteria cut-off for establishing ovulation and assessing the sensitivity, specificity and accuracy values of the method. Methodology: Twenty-one professional and semi-professional, Spanish league female football players (18.6 ± 1.5 years, 58.1 ± 6.0 kg, 164.0 ± 4.8 cm) with natural menstrual cycles, completed the study. Capillary blood and saliva samples were collected from each participant on twelve occasions each separated by at least 7 days. All samples were collected in the morning, following an overnight fast. Results: According to luteal phase serum progesterone concentrations, 11 out of 21 (52%) players presented with menstrual irregularities (oligomenorrheic n = 6, anovulatory n = 4, amenorrhoeic n = 1). A significant correlation was observed between plasma and saliva progesterone in the estimated eumenorrheic group (r = 0.80, p = <0.001, 95% CI 0.72-0.86). The association between serum and saliva progesterone was weaker in the oligomenorrheic group (r = 0.47, p = <0.001, 95% CI 0.27-0.64) and was not present in the anovulatory or amenorrhoeic groups. Conclusions: Salivary measurements of progesterone are well correlated with capillary blood when taken during eumenorrheic menstrual cycles and presents a viable, non-invasive method of establishing characteristic progesterone fluctuations in applied sport settings. The strength of the association appears to be concentration dependent. A luteal phase saliva progesterone (P4) >50 pg/ml and >1.5× follicular baseline has good sensitivity, specificity, and accuracy to indicate ovulation compared to established criteria for serum progesterone.

The impact of sex hormones on metabolic syndrome: univariable and multivariable Mendelian randomization studies.

BACKGROUND: Observational studies have found associations between sex hormones and metabolic syndrome(Mets), but the causal relationships remains unclear. This study utilizes univariable and multivariable Mendelian randomization (MR) to elucidate the associations between sex hormones (including sex hormone-binding globulin(SHBG), estradiol(E2), testosterone(T)) and Mets and its subtypes (including waist circumference(WC), fasting blood glucose(FBG), high blood pressure(HBP), high-density lipoprotein(HDL-C), triglycerides(TG)). METHODS: We utilized summary data from large-scale genome-wide association studies. Univariable Mendelian randomization (UMVMR) analysis was primarily conducted using the inverse variance weighted method (IVW), with secondary analyses employing the weighted median, MR-Egger regression, simple mode method, and weighted mode method. Subsequently, multivariable Mendelian randomization (MVMR) was employed to assess the causal relationships between SHBG, T, E2, and MetS and its components: WC, FPG, HBP, HDL-C, and TG. Sensitivity analyses were conducted to assess result reliability. RESULTS: Genetically predicted SHBG was significantly negatively associated with MetS (UMVMR: ß=-0.72; 95% CI = 0.41 to 0.57; P = 1.28e-17; MVMR: ß=-0.60; 95% CI=-0.83 to -0.38; P < 0.001). Positive causal relationships were observed between SHBG and WC(MVMR: ß = 0.10; 95% CI = 0.03 to 0.17; P = 0.01) and HDL-C (MVMR: ß = 0.41; 95% CI = 0.21 to 0.60; P < 0.001), while negative causal relationships were found between SHBG and HBP (MVMR: ß=-0.02; 95% CI=-0.04 to -0.00; P = 0.02), TG (MVMR: ß=-0.48; 95% CI=-0.70 to -0.26; P < 0.001). Genetically predicted E2 exhibited a negative association with TG (MVMR: ß=-1.49; 95% CI=-2.48 to -0.50; P = 0.003). Genetically predicted T was negatively associated with TG (MVMR: ß=-0.36; 95% CI=-0.71 to -0.00; P = 0.049) and WC (MVMR: ß=-0.13; 95% CI=-0.24 to -0.02; P = 0.02), with inconsistent sensitivity analyses. Additionally, No other causal associations were found. CONCLUSION: Our study indicates that SHBG is a protective factor for MetS, potentially delaying its onset and progression through improvements in HBP and TG. Furthermore, T and E2 may improve TG levels, with T also reducing WC levels. Importantly, our study provides new insights for the prevention and treatment of MetS.

Maternal preconception glucose intolerance and fatty acid intake from conception to weaning: impact on offspring energy homeostasis in both male and female.

Environmental factors in the early life stages can lead the descendant to adaptations in gene expression, permanently impacting several structures and organs. The amount and quality of fatty acids in the maternal diet in pregnancy and lactation were found to impact offspring metabolism. So, maternal diet and insulin resistance can affect the male and female descendants through distinct pathways and at different time points. We hypothesized that maternal high-fat diet (HFD) intake before conception and an adequate amount of different fatty acids intake during pregnancy and lactation could influence the energy homeostasis system of 21-day-old offspring. Female rats received control diet (C) or HFD (HF) for 8 weeks before pregnancy. During pregnancy and lactation C group remained with same diet (C-C), HF group were distributed into 4 groups and received C diet (HF-C), normolipidic diet based on saturated fatty acids (HF-S) or based on polyunsaturated fatty acids n-3 (HF-P) or remained in same diet (HF-HF). Maternal HFD in preconception, pregnancy, and lactation (HF-HF) led to lower glucagon-like peptide-1 levels in male (HF-HF21) compared to other groups (C-C21, HF-C21, and HF-P21) and compared to HF-HF21 females. Neuropeptide YY levels were higher in the HF-HF21, HF-C21, and HF-S21 male offspring compared to HF-P21. HF-P21 was similar to C-C21. Positive correlations were found among the energy homeostasis markers genes expressed in the offspring hypothalamus. Maternal diet changes to adequate quantities of fatty acids during pregnancy and lactation showed less impaired results but was not entirely avoided. A maternal diet based on PUFA n-3 during pregnancy and lactation seems to reverse the damage of an HFD in preconception. These results of homeostasis energy system disturbance in the offspring at weaning give us clues about changes that precede the onset of the disease in adult life - adding notes to the knowledge for future investigations of prevention and treatment of chronic diseases.

Insights into the structure and activation mechanism of some class B1 GPCR family members.

In humans, 15 genes encode the class B1 family of GPCRs, which are polypeptide hormone receptors characterized by having a large N-terminal extracellular domain (ECD) and receive signals from outside the cell to activate cellular response. For example, the insulinotropic polypeptide (GIP) stimulates the glucose-dependent insulinotropic polypeptide receptor (GIPR), while the glucagon receptor (GCGR) responds to glucagon by increasing blood glucose levels and promoting the breakdown of liver glycogen to induce the production of insulin. The glucagon-like peptides 1 and 2 (GLP-1 and GLP-2) elicit a response from glucagon-like peptide receptor types 1 and 2 (GLP1R and GLP2R), respectively. Since these receptors are implicated in the pathogenesis of diabetes, studying their activation is crucial for the development of effective therapies for the condition. With more structural information being revealed by experimental methods such as X-ray crystallography, cryo-EM, and NMR, the activation mechanism of class B1 GPCRs becomes unraveled. The available crystal and cryo-EM structures reveal that class B1 GPCRs follow a two-step model for peptide binding and receptor activation. The regions close to the C-termini of hormones interact with the N-terminal ECD of the receptor while the regions close to the N-terminus of the peptide interact with the TM domain and transmit signals. This review highlights the structural details of class B1 GPCRs and their conformational changes following activation. The roles of MD simulation in characterizing those conformational changes are briefly discussed, providing insights into the potential structural exploration for future ligand designs.